Intake of Flavonoids and Lung Cancer

Marchand, Loı̈c Le; Murphy, Suzanne P.; Hankin, Jean H.; Wilkens, Lynne R.; Kolonel, Laurence N.

doi:10.1093/jnci/92.2.154

Cited by 511 publications

(345 citation statements)

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“…For example, chronic quercetin treatment was shown to lower blood pressure or prevent the development of hypertension in various experimental models [Duarte et al, 2001;Perez-Vizcaino et al, 2006]. Consumption of quercetin, enriched in onions and apples, was found to be inversely associated with lung cancer risk [Le Marchand et al, 2000]. Furthermore, quercetin was shown to inhibit cancer growth and induce apoptosis in animal models [Mouria et al, 2002].…”

Section: Discussionmentioning

confidence: 99%

Quercetin sensitizes human hepatoma cells to TRAIL‐induced apoptosis via Sp1‐mediated DR5 up‐regulation and proteasome‐mediated c‐FLIP_S down‐regulation

Kim

Park

et al. 2008

J of Cellular Biochemistry

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This study demonstrates that combined treatment with subtoxic doses of quercetin (3 0 ,3 0 ,4 0 ,5,7-pentahydroxyflavone), a flavonoid found in many fruits and vegetables, plus tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces rapid apoptosis in TRAIL-resistant hepatocellular carcinoma (HCC) cells. Effective induction of apoptosis by the combined treatment with quercetin and TRAIL was not blocked by overexpression of Bcl-xL, which is known to confer resistance to various chemotherapeutic agents. These results suggest that this combined treatment may provide an attractive strategy for treating resistant HCCs. While the proteolytic processing of procaspase-3 by TRAIL was partially blocked in various HCC cells treated with TRAIL alone, co-treatment with quercetin efficiently recovered TRAIL-induced caspase activation. We found that quercetin treatment of HCC cells significantly up-regulated the mRNA and protein levels of DR5, a death receptor of TRAIL, in a transcription factor Sp1-dependent manner. Furthermore, treatment with quercetin significantly decreased the protein levels of c-FLIP, an inhibitor of caspase-8, through proteasome-mediated degradation. Finally, administration of small interfering RNA against DR5 or overexpression of c-FLIP S , but not c-FLIP L , significantly attenuated quercetin-stimulated TRAIL-induced apoptosis. Collectively, these findings show that quercetin recovers TRAIL sensitivity in various HCC cells via up-regulation of DR5 and down-regulation of c-FLIP S . J. Cell. Biochem. 105: 1386-1398. ß 2008 KEY WORDS: QUERCETIN; TRAIL; HEPATOMA; DR5; c-FLIP S H epatocellular carcinoma (HCC) is the fifth most frequent neoplasm worldwide (>500,000 death/year) [Bruix et al., 2004]. Most hepatocellular carcinoma patients are diagnosed at advanced stages that are unsuitable for the current curative therapies of resection and transplantation [Avila et al., 2006]. The current chemotherapeutic options yield poor responses and low patient survival, making them ineffective for treatment of advanced HCC [Avila et al., 2006]. Therefore, new therapeutic alternatives are needed for more effective treatment of this malignancy.Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF family, is considered a promising anticancer agent due to its ability to induce apoptosis in a variety of tumor cell types while having only negligible effects on normal cells [Ashkenazi et al., 1999]. Binding of TRAIL to either DR4 or DR5, two death receptors of TRAIL, leads to oligomerization and clustering of their intracellular death domains. The subsequent interaction of DR4 or DR5 with the adaptor molecule, FADD (Fas-associated death domain), via their respective death domains leads to recruitment and activation of caspase-8 [ Thomas et al., 2004]. Finally, caspase-8 activates the executioner caspases (e.g., caspase-3 and caspase-7), leading to apoptotic cell death [Srivastava, 2001]. Although TRAIL has garnered considerable attention as a novel anticancer agent...

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Section: Discussionmentioning

confidence: 99%

Quercetin sensitizes human hepatoma cells to TRAIL‐induced apoptosis via Sp1‐mediated DR5 up‐regulation and proteasome‐mediated c‐FLIP_S down‐regulation

Kim

Park

et al. 2008

J of Cellular Biochemistry

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“…General characteristics of case-control and cohort studies are shown in Tables 1 and 2, respectively. Case-control studies were published between 1994 and 2014; three were conducted in Italy (13,19,22) , two each in Iran (10,15) , China (12,23) and Australia (14,29) , and one each in Poland (16) , Spain (11) , Czech Republic (17) , Brazil (18) , UK (20) , India (24) , Hawaii (25) , Mexico (26) , Sweden (27) and Uruguay (28) . One was a multinational study conducted in nine countries worldwide (Italy, Spain, Poland, Northern Ireland, India, Cuba, Canada, Australia and Sudan) (21) Cohort studies were published between 1998 and 2012; nine were conducted in the USA (30,31,(34)(35)(36)(37)39,40,45) and eight were conducted in Europe (32,33,38,(41)(42)(43)(44)46) .…”

Section: Literature Searchmentioning

confidence: 99%

Apple intake and cancer risk: a systematic review and meta-analysis of observational studies

Fabiani

Minelli

Rosignoli

2016

Public Health Nutr.

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Objective: Conflicting results on the association between fruit consumption and cancer risk have been reported. Little is known about the cancer preventive effects of different fruit types. The present meta-analysis investigates whether an association exists between apple intake and cancer risk. Design: Relevant observational studies were identified by literature search (PubMed, Web of Science and Embase). A random-effect model was used to estimate the cancer risk in different anatomical sites. Between-study heterogeneity and publication bias were assessed using adequate statistical tests. Results: Twenty case-control (three on lung, five on colorectal, five on breast, two on oesophageal, three on oral cavity, two on prostate and one each on pancreas, bladder, larynx, ovary, kidney and brain cancer) and twenty-one cohort (seven on lung, two on colorectal, three on breast and one each on oesophageal, pancreas, bladder, kidney, endometrial, head-neck, urothelial and stomach cancer) studies met the inclusion criteria. Comparing the highest v. lowest level of apple consumption, the reduction of lung cancer risk was statistically highly significant in both case-control (OR = 0·75; 95 % CI 0·63, 0·88; P = 0·001, I 2 = 0 %) and cohort studies (relative risk = 0·89; 95 % CI 0·84, 0·94; P < 0·001, I 2 = 53 %). Instead, in the case of colorectal (OR = 0·66; 95 % CI 0·54, 0·81; P < 0·001, I 2 = 55 %), breast (OR = 0·79; 95 % CI 0·73, 0·87; P < 0·001, I 2 = 1 %) and overall digestive tract (OR = 0·50; 95 % CI 0·36, 0·69; P < 0·001, I 2 = 90 %) cancers a significant preventive effect of apples was found only in case-control studies while prospective studies indicated no effect. No evidence of publication bias could be detected for colorectal, oral cavity, oesophageal and breast cancer. However, some confounding effects may be present and related to the consumption of other fruit which have not been considered as adjusting factors. Conclusions: The present meta-analysis indicates that consumption of apples is associated with a reduced risk of cancer in different anatomical sites. Keywords Cancer preventionApple intake Dietary Epidemiology Meta-analysis Cancer is a chronic degenerative disease causing major morbidity and mortality in Western countries. It has been estimated that in the year 2012, 14·1 million new cancer cases were diagnosed and 8·2 million cancer deaths were established (1) . The overall age-standardized cancer incidence rates vary three-to fivefold across different regions of the world (2) . These variations may be related to different modifiable risk and preventive factors among which diet may play a central role. It has been estimated that about one-third of all cancer could be avoidable by changes in eating habits (3) .Foods of plant origin have received particular interest over the years as potential cancer-preventive components of a healthy diet. Fruit and vegetables contain a myriad of bioactive phytochemicals that, through various molecular mechanisms, show chemopreventive properties in both in...

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“…Previous studies have indicated that naringenin has anti-cancer effects; however most studies focused on its role in primary tumor prevention (So et al, 1996;Le Marchand et al, 2000;Kanno et al, 2005), and few investigated its antimetastatic effects. We previously found that naringenin could attenuate bleomycin-induced pulmonary fibrosis by improving the immunosuppressive environment .…”

Section: Introductionmentioning

confidence: 99%

Naringenin reduces lung metastasis in a breast cancer resection model

Qin

Jin

et al. 2011

Protein Cell

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Metastasis is the main cause of death in cancer patients. To improve the outcomes of patients undergoing a surgery, new adjuvant therapies that can effectively inhibit metastases have to be developed. Studies have shown that flavonoid naringenin, a natural product that is mainly present in grapes and citrus, may contribute to cancer prevention. It has many advantages compared to traditional chemotherapeutic drugs, such as low toxicity. To determine whether naringenin can also inhibit metastases, a breast cancer resection model that mimics clinical situations was established. We found that orally administered naringenin significantly decreased the number of metastatic tumor cells in the lung and extended the life span of tumor resected mice. Flow cytometry analysis revealed that T cells displayed enhanced antitumor activity in naringenin treated mice, with an increased proportion of IFN-γ and IL-2 expressing T cells. In vitro studies further demonstrated that relief of immunosuppression caused by regulatory T cells might be the fundamental mechanism of metastasis inhibition by naringenin. These results indicate that orally administered naringenin can inhibit the outgrowth of metastases after surgery via regulating host immunity. Thus, naringenin can be an ideal surgical adjuvant therapy for breast cancer patients.

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Intake of Flavonoids and Lung Cancer

Abstract: If replicated, particularly in prospective studies, these findings would suggest that foods rich in certain flavonoids may protect against certain forms of lung cancer and that decreased bioactivation of carcinogens by inhibition of CYP1A1 should be explored as underlying mechanisms.

Cited by 511 publications

References 43 publications

Quercetin sensitizes human hepatoma cells to TRAIL‐induced apoptosis via Sp1‐mediated DR5 up‐regulation and proteasome‐mediated c‐FLIP_S down‐regulation

Quercetin sensitizes human hepatoma cells to TRAIL‐induced apoptosis via Sp1‐mediated DR5 up‐regulation and proteasome‐mediated c‐FLIP_S down‐regulation

Apple intake and cancer risk: a systematic review and meta-analysis of observational studies

Naringenin reduces lung metastasis in a breast cancer resection model

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Intake of Flavonoids and Lung Cancer

Abstract: If replicated, particularly in prospective studies, these findings would suggest that foods rich in certain flavonoids may protect against certain forms of lung cancer and that decreased bioactivation of carcinogens by inhibition of CYP1A1 should be explored as underlying mechanisms.

Cited by 511 publications

References 43 publications

Quercetin sensitizes human hepatoma cells to TRAIL‐induced apoptosis via Sp1‐mediated DR5 up‐regulation and proteasome‐mediated c‐FLIPS down‐regulation

Quercetin sensitizes human hepatoma cells to TRAIL‐induced apoptosis via Sp1‐mediated DR5 up‐regulation and proteasome‐mediated c‐FLIPS down‐regulation

Apple intake and cancer risk: a systematic review and meta-analysis of observational studies

Naringenin reduces lung metastasis in a breast cancer resection model

Contact Info

Product

Resources

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Quercetin sensitizes human hepatoma cells to TRAIL‐induced apoptosis via Sp1‐mediated DR5 up‐regulation and proteasome‐mediated c‐FLIP_S down‐regulation

Quercetin sensitizes human hepatoma cells to TRAIL‐induced apoptosis via Sp1‐mediated DR5 up‐regulation and proteasome‐mediated c‐FLIP_S down‐regulation